In vivo human pharmacodynamics of the psychodysleptic 4-Br-2,5- dimethoxyphenylisopropylamine labelled with $sup 82$Br or $sup 77$Br
The psychodysleptic compound 4-Br-2,5-dimethoxyphenylisopropylamine (4- Br-DPIA) was synthesized with $sup 82$Br or $sup 77$Br and administered to five human subjects in three oral and three intravenous experiments. In vivo organ concentrations were measured by gamma ray scintigraphy with computerized area integration, and by whole-body counting. Urine was analyzed by solvent separation, and thin layer chromatography of dansylated metabolites. The urine contained less than 5 percent radiobromine precipitate by acidic AgNO$sub 3$, demonstrating that the Br label remained organically bound. Upon intravenous administration radioactivity appeared immediately in the lungs by first-pass extraction, was rapidly released and reached maximum concentrations in the liver at 0.5 to 1.5 hr, plasma at 2 to 3 hr and brain at 3 to 6 hr. Orally the pattern was the same except that the initial lung concentration did not occur. This sequence of maximum organ concentrations suggests that a metabolite of 4-Br-DPIA is the centrally active compound which concentrates in the brain. Solvent separation of urine showed 81.8 percent of metabolites to be aqueous soluble and 12.5 percent free base; slower whole-body excretion correlated with higher levels of free base in the urine. The methods used demonstrate a new approach to the study of in vivo distribution and kinetics of drugs which can be labelled with gamma-emitting radioisotopes. (auth)
- Research Organization:
- Univ. of California, Berkeley
- NSA Number:
- NSA-33-007701
- OSTI ID:
- 4147158
- Journal Information:
- Neuropharmacology, v. 14, pp. 165-174, Journal Name: Neuropharmacology, v. 14, pp. 165-174; ISSN NEPHB
- Country of Publication:
- United Kingdom
- Language:
- English
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